Pflegel P, Klaus T, Schöbel H, Gruno M
Fachbereich Pharmazie, Ernst-Moritz-Arndt-Universität Greifswald.
Pharmazie. 1993 Oct;48(10):741-4.
A method for determination of drug substances solubility in lipophilic solvents is presented. The solubility was determined in lipophilic suppository bases meltings, in pharmaceutical lipoids as Oleum Ricini, Oleum Arachidis, Cera perliquida, Paraffinum perliquidum and in chemically defined lipoids as n-hexadecane, 1-hexadecane, cetylic alcohol, palmitic acid, cetylpalmitate. Consequences from chemical constitution of substances for solubility are discussed, also consequences from chemical constitution and dielectric constants of lipoidic solvents for their solution behavior. For the substances investigated, the apparent partition coefficients in the two-phase systems lipoid/phosphate buffer pH 7,4 and n-octanol/phosphate buffer pH 7,4 were determined, also the solubility in phosphate buffer. The results show, that connections between partition coefficients and solubility in lipophilic or aqueous phases do not exist. On the other hand, an indirect proportionality between water solubility and lipoid solubility also does not exist. In consequence, interpretations of drug release from lipophilic systems have to be proceeded from exact knowledge of partition behavior and solubilities in both the lipophilic and aqueous phase.
介绍了一种测定药物物质在亲脂性溶剂中溶解度的方法。测定了药物物质在亲脂性栓剂基质熔融物中、在药用类脂如蓖麻油、花生油、液状石蜡、液体石蜡中的溶解度，以及在化学定义的类脂如正十六烷、1 - 十六烷、鲸蜡醇、棕榈酸、十六烷基棕榈酸酯中的溶解度。讨论了物质化学组成对溶解度的影响，以及类脂溶剂的化学组成和介电常数对其溶解行为的影响。对于所研究的物质，测定了在类脂/ pH 7.4磷酸盐缓冲液和正辛醇/ pH 7.4磷酸盐缓冲液两相系统中的表观分配系数，以及在磷酸盐缓冲液中的溶解度。结果表明，分配系数与在亲脂相或水相中的溶解度之间不存在关联。另一方面，水溶性与类脂溶解度之间也不存在间接比例关系。因此，对亲脂性系统中药物释放的解释必须基于对亲脂相和水相中分配行为及溶解度的确切了解。
